Table 4

Relations between CYP2C19, CYP2D6, CYP3A5 and SULT1A1 genotypes and tamoxifen and its metabolites in postmenopausal women (n = 90)

Median concentration [q1 - q3] 1


Genotype (n)

tamoxifen

4OHtam

4OHNDtam

NDtam

NDDtam

tamNox


CYP2C192

*2/*2

(4)

107 [79 - 137]

5.1 [3.3 - 5.2]

45.7 [41.3 - 54.7]

263 [156 - 404]

47.0 [39.0 - 67.4]

12.8 [10.3 - 31.8]

*1/*2

(15)

107 [79 - 140]

5.8 [5.1 - 8.9]

61.2 [43.2 - 83.9]

233 [194 - 322]

44.8 [40.2 - 71.4]

9.7 [8.5 - 16.5]

*1/*1

(35)

92 [79 - 118]

5.5 [4.6 - 6.8]

49.6 [44.7 - 61.6]

231 [190 - 357]

38.1 [26.7 - 46.4]

9.5 [7.4 - 12.7]

Vt*17

(33)

95 [76 - 126]

6.1 [5.0 - 7.4]

53.3 [41.4 - 67.4]

229 [196 - 319]

37.8 [25.6 - 55.1]

9.1 [6.3 - 10.8]

*17/*17

(3)

154 [31 - 157]

11.3 [3.0 - 17.2]

94.3 [34.0 - 184.8]

341 [142 - 438]

36.9 [15.7 - 79.0]

11.1 [3.5 - 11.7]

P3

0.371

0.240

0.652

0.600

0.022*

0.002**

CYP2D64

PM

(6)

85 [58 - 125]

4.0 [3.1 - 5.5]

37.4 [31.8 - 48.2]

296 [179 - 444]

47.0 [22.8 - 55.9]

9.2 [6.1 - 21.0]

IM

(32)

87 [78 - 141]

5.9 [4.6 - 6.9]

50.5 [38.6 - 62.8]

243 [217 - 358]

38.2 [24.9 - 44.7]

9.4 [7.1 - 11.0]

Wt/Wt

(51)

99 [80 - 124]

6.1 [5.0 - 8.1]

55.5 [45.7 - 69.7]

223 [117 - 299]

40.4 [33.0 - 55.6]

9.8 [7.4 - 13.4]

UM

(1)

107

5.8

46.3

185

40.3

9.0

P

0.358

0.019*

0.009**

0.044*

0.413

0.958

CYP3A5

Vt/Vt

(76)

96 [75 - 127]

5.6 [4.7 - 7.0]

49.9 [41.3 - 65.5]

228 [189 - 316]

38.4 [27.0 - 51.4]

9.4 [6.9 - 11.8]

Wt/Vt

(14)

102 [81 - 162]

6.8 [5.7 - 10.2]

54.6 [49.4 - 80.6]

297 [221 - 396]

45.7 [32.7 - 67.3]

12.0 [9.7 - 14.5]

P

0.203

0.074

0.154

0.075

0.052

0.044*

SULT1A1

Vt/Vt

(14)

91 [68 - 138]

5.5 [4.1 - 7.5]

48.6 [40.4 - 60.7]

228 [185 - 353]

37.1 [23.4 - 49.8]

9.3 [6.9 - 11.8]

Wt/Vt

(32)

103 [90 - 141]

6.0 [5.1 - 7.3]

58.5 [46.2 - 75.3]

244 [201 - 361]

44.8 [37.9 - 57.6]

10.7 [8.7 - 15.2]

Wt/Wt

(44)

87 [80 - 105]

5.4 [4.6 - 8.9]

51.3 [40.8 - 73.5]

219 [183 - 294]

36.9 [25.7 - 49.4]

9.0 [6.8 - 10.1]

P

0.649

0.512

0.286

0.755

0.197

0.712

SULT1A1copy numbers

1

(3)

84 [80 - 168]

6.7 [6.1 - 8.9]

55.1 [49.0 - 85.0]

278 [217 - 364]

37.9 [24.2 - 60.4]

9.7 [6.9 - 10.6]

2

(59)

92 [68 - 123]

5.6 [4.6 - 6.8]

50.5 [41.2 - 64.4]

227 [188 - 299]

38.4 [27.7 - 47.9]

9.4 [6.6 - 11.7]

3

(21)

107 [87 - 162]

6.9 [5.2 - 9.8]

52.7 [46.6 - 80.2]

271 [198 - 395]

46.5 [33.0 - 59.2]

9.8 [8.3 - 13.8]

4

(5)

103 [82 - 139]

5.1 [4.2 - 7.5]

58.6 [39.1 - 71.7]

223 [205 - 346]

38.1 [28.4 - 62.3]

12.7 [8.4 - 14.5]

5

(2)

86 [51 - 122]

6.2 [4.1 - 8.4]

49.2 [32.4 - 66.1]

260 [150 - 371]

45.1 [23.1 - 67.2]

11.7 [5.6 - 17.7]

P4

0.352

0.863

0.719

0.475

0.370

0.280


1Median concentration [quartile 1 - quartile 3] values of tamoxifen and metabolites are given as ng/ml.

2*2/*2, encodes defective CYP2C19 activity; Vt*17, subjects heterozygous for the variant type allele CYP2C19*17 (*1/*17 and *2/*17); *17/*17, encodes ultra rapid CYP2C19 activity.

3P values were calculated by multivariate logistic regression model, *p < 0.05. Adjusted for CYP2C19, CYP2D6, CYP3A5, SULT1A1, SULT1A1 copy number, FSH and SHBG.

4PM, poor metabolizer; IM, wild type/variant type; Wt/Wt, wild type/wild type; UM, ultra rapid metabolizer.

Gjerde et al. BMC Cancer 2010 10:313   doi:10.1186/1471-2407-10-313

Open Data